This multicenter, randomized, controlled clinical trial assessed the influence of sodium chloride intake on the antihypertensive effect of the calcium channel blocker isradipine. Participants with uncomplicated hypertension controlled by isradipine entered a 4-week sodium-restricted (60 to 80 mmol/24 h) period. Participants with urinary sodium levels < 120 mmol/24 h (n = 99) were randomized to placebo or sodium chloride (100 mmol/24 h) for 4 weeks, and then crossed over to the alternative treatment for an additional 4 weeks. Mean baseline systolic blood pressure was 151.9 ± 16.7 mm Hg (mean ± SD). During open-label isradipine treatment, systolic blood pressures for ad libitum sodium chloride and restriction were 134.1 ± 11.1 and 132.1 ± 12.2 mm Hg respectively; for double-blind sodium chloride restriction and supplementation: 133.6 ± 12.6 and 138.5 ± 12.8 mm Hg (P < .01). Urinary sodium excretion values for open-label isradipine ad libitum versus restricted were 140.6 ± 61.9 versus 76.9 ± 32.4 mmol/24 h; for double-blind restricted versus supplemented, sodium excretion was 120.5 ± 68.9 v 175.9 ± 68.7 mmol/24 h (P ≤ .0001). Changes in urinary sodium excretion were not predictive of variations in blood pressure. Urinary sodium excretion during sodium restriction correlated directly with HDL-cholesterol (P < .02) and inversely with total cholesterol:HDL-cholesterol (P = .02), despite decreased total and saturated fat intake (P < .01). Sodium restriction was associated with significant reductions (P < .01) in virtually all macronutrients and electrolytes, and thus had an adverse impact on overall nutrition. The antihypertensive action of isradipine was not enhanced by dietary sodium chloride restriction, and the lipoprotein proble was least favorable with sodium chloride restriction.